Pro-Inflammatory Alterations of Circulating Monocytes in Latent Tuberculosis Infection.

Background: Latent tuberculosis infection (LTBI) has been associated with increased cardiovascular risk. We investigated the activation and pro-inflammatory profile of monocytes in individuals with LTBI and their association with coronary artery disease (CAD). Methods: Individuals 40-70 years old in Lima, Peru, underwent QuantiFERON-TB testing to define LTBI, completed a coronary computed tomography angiography to evaluate CAD, and provided blood for monocyte profiling using flow cytometry. Cells were stimulated with lipopolysaccharide to assess interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α responses. Results: The clinical characteristics of the LTBI (n = 28) and non-LTBI (n = 41) groups were similar. All monocyte subsets from LTBI individuals exhibited higher mean fluorescence intensity (MFI) of CX3CR1 and CD36 compared with non-LTBI individuals. LTBI individuals had an increased proportion of nonclassical monocytes expressing IL-6 (44.9 vs 26.9; P = .014), TNF-α (62.3 vs 35.1; P = .014), and TNF-α+IL-6+ (43.2 vs 36.6; P = .042). Among LTBI individuals, CAD was associated with lower CX3CR1 MFI on classical monocytes and lower CD36 MFI across all monocyte subsets. In multivariable analyses, lower CD36 MFI on total monocytes (b = -0.17; P = .002) and all subsets remained independently associated with CAD in LTBI. Conclusions: Individuals with LTBI have distinct monocyte alterations suggestive of an exacerbated inflammatory response and tissue migration. Whether these alterations contribute to cardiovascular disease pathogenesis warrants further investigation.

Predictive value of incidental right ventricular abnormalities identified on SPECT for mortality and pulmonary hypertension.

BACKGROUND: The clinical significance of incidentally found RV abnormalities on low-risk SPECT studies is not well-defined. The objective of this study was to determine the predictive value of incidental right ventricular (RV) abnormalities identified on single photon emission computed tomography (SPECT) scans for mortality and pulmonary hypertension (PH). METHODS: We retrospectively analyzed all low-risk SPECT studies in patients without known coronary artery or pulmonary vascular disease, performed at our institution, from 2007-2020. Adjusted Cox proportional hazards models were used to evaluate the association between incidental RV abnormalities on low-risk SPECT studies and outcomes. RESULTS: Of the 4761 patients included in the analysis, mortality events were present in 494, and echocardiographic PH was present in 619. Incidental RV abnormalities on low-risk SPECT studies were significantly and independently associated with all-cause mortality (HR = 1.41, CI [1.07-1.86], P = 0.0152) and echocardiographic PH (HR = 2.06, CI [1.64-2.60], P < 0.0001). CONCLUSIONS: These data suggest incidental RV abnormalities found on low-risk SPECT imaging studies are significantly and independently associated with increased mortality and risk of developing echocardiographic PH, and could identify high-risk patients for closer monitoring and additional diagnostic testing.

Leveraging copper import by yersiniabactin siderophore system for targeted PET imaging of bacteria.

There is an emerging need for accurate and rapid identification of bacteria in the human body to achieve diverse biomedical objectives. Copper homeostasis is vital for the survival of bacterial species owing to the roles of the metal as a nutrient, respiratory enzyme cofactor, and a toxin. Here, we report the development of a copper-64-labeled bacterial metal chelator, yersiniabactin, to exploit a highly conserved metal acquisition pathway for noninvasive and selective imaging of bacteria. Compared with traditional techniques used to manufacture probes, our strategy simplifies the process considerably by combining the function of metal attachment and cell recognition to the same molecule. We demonstrate, for the first time to our knowledge, how a copper-64 PET probe can be used to identify specific bacterial populations, monitor antibiotic treatment outcomes, and track bacteria in diverse niches in vivo.

Cardiac magnetic resonance imaging as a prognostic biomarker in treatment-naïve pulmonary hypertension.

PURPOSE: Targeted treatment for pulmonary arterial hypertension (PAH), diagnosed via right heart catheterization (RHC), has been shown to improve morbidity and mortality. Identifying characteristics that predict clinical worsening has been challenging. We sought to evaluate the role of cardiac Magnetic Resonance Imaging (CMR) as a predictor of clinical worsening in a cohort of treatment-naïve pulmonary hypertension (PH) patients. METHODS: We performed a retrospective single center analysis of all adults with newly diagnosed treatment-naïve PH between January 1st 2013 and January 1st 2019. Patients with World Health Organization (WHO)-Group I PAH or WHO-Group II/III PH disease, who underwent both CMR (Signa Horizon 1.5 T, General Electric, Milwaukee, WI and Siemens Espree 1.5 T, Munich, Germany) and RHC testing prior to targeted PAH treatment, were included for analysis. Cox proportional hazards models were constructed. RESULTS: A total of 38 patients, of which 12 (32 %) experienced the primary outcome of clinical worsening. were included in the final analysis, Patients with clinical worsening were significantly more likely to have RV dysfunction by CMR (including lower RV ejection fraction (HR 0.93, p = 0.007) and more RV dilation (HR 1.02, p = 0.005-0.021)) and RHC (including worse pulmonary vascular resistance (HR 1.32, p < 0.001)), even after adjustment for disease severity. Both CMR and RHC measures of RV dysfunction were found to be equally effective in predicting clinical worsening, regardless of PH etiology. CONCLUSIONS: In treatment-naïve PH patients, including those with WHO-Group II/III disease, both CMR and RHC measures independently and significantly predicted clinical worsening, even after adjustment for disease severity.

The role of lysyl oxidase family members in the stabilization of abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAAs) are a major cause of morbidity and mortality in the United States today. We employed a model for AAA development using apolipoprotein E knock out mice fed a high-fat diet and treated with ANG II and ß-aminopropionitrile (ß-APN) for 4 wk. ANG II induces hypertension and atherosclerotic disease, whereas ß-APN inhibits the activity of the lysyl oxidase/ lysyl oxidase-like protein (LOX/LOXL) family members. LOX/LOXL family members crosslink collagen and elastin in the extracellular matrix and therefore contribute to the integrity and stabilization of a healthy vessel wall. In this model, cotreatment with ANG II and ß-APN caused a 90% AAA incidence and increased atherosclerotic lesion formation from less than 5% to greater than 25% after 4 wk. In more atheroprotected mouse strains (C57BL/6 and BalbC), cotreatment with ANG II and ß-APN caused 50% and 40% AAA incidence, respectively. These data demonstrate the importance of LOX/LOXL to the stability of the vessel wall. Therapeutic strategies to overexpress LOX/LOXL enzymes or to support the crosslinking of soluble matrix proteins in a polymeric scaffold are a promising opportunity to achieve stabilization of AAAs.

Time-resolved analysis of coronary vein motion and cross-sectional area.

PURPOSE: To quantify periods of low motion and cross-sectional area changes of the coronary veins during the cardiac cycle for planning magnetic resonance coronary venograms (MRCV). MATERIALS AND METHODS: Images were acquired from 19 patients with coronary artery disease (CAD) and 13 patients scheduled for cardiac resynchronization therapy (CRT). The displacement and cross-sectional area of the coronary sinus was tracked, and periods of low motion were defined as consecutive time points during which the position of the coronary sinus remained within a 0.67-mm diameter region. Patients were classified as systolic dominant or diastolic dominant based on the relative duration of their low motion periods. RESULTS: All CRT patients were classified as systolic dominant, and 32% of these had no separate diastolic rest period. All CAD patients with ejection fraction < 35% were classified as systolic dominant, while all CAD patients with ejection fraction > 35%were diastolic dominant. In 77% of all subjects, the cross-sectional area of the coronary sinus was larger in systole than in diastole. CONCLUSION: The movement of the coronary sinus can be used to classify patients as either having a longer systolic or diastolic rest period. The classification of the CRT patients as systolic dominant suggests that MRCVs be acquired in systole for CRT planning; however, each patient's low motion periods should be categorized to ensure the correct period is being used to minimize motion artifacts.

Influence of symptomatic status on the prevalence of obstructive coronary artery disease in patients with zero calcium score.

BACKGROUND: CAC has been used to predict obstructive CAD on invasive coronary angiography. However, it is unknown how the prevalence of obstructive CAD in patients with zero CAC is influenced by the presence or absence of chest pain. METHODS: 210 consecutive patients referred for CAC and CorCTA were included in this analysis. Chest pain was defined based on the Diamond-Forrester classification. RESULTS: 134 patients (64%) were symptomatic and 76 (36%) were asymptomatic. Seventy patients had negative (33%); 140 had positive CAC (67%). In the symptomatic group with zero CAC, 8.2% (4/49) had an obstructive, non-calcified plaque; of these, 3 were <45 years. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CAC in the symptomatic population for detection of obstructive CAD were 0.86 (0.66-0.95), 0.42 (0.33-0.52), 0.28 (0.19-0.39) and 0.92 (0.8-0.97), respectively (p=0.007). No asymptomatic subject with zero CAC had obstructive CAD. Sensitivity, specificity, PPV and NPV of CAC in the asymptomatic population for detection of obstructive CAD were 1.00 (0.66-1.00), 0.32 (0.21-0.45), 0.18 (0.10-0.31) and 1.00 (0.80-1.00), respectively (p=0.05). Optimal cut-points to predict obstructive CAD and AUC were significantly different in symptomatic versus asymptomatic subjects (91 and 0.78 vs. 296 and 0.89, respectively) (p=0.005). CAC performed much better in symptomatic patients >45 years compared to younger patients to exclude obstructive CAD (AUC: 0.83 vs. 0.5, p<0.001; NPV=0.98). CONCLUSIONS: CAC is better in asymptomatic compared to symptomatic subjects, especially in patients